POS0429 THE COMPLEMENT SYSTEM AND RESPONSE TO TNF INHIBITION IN PATIENTS WITH RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS. POST HOC ANALYSIS FROM CONSUL, A LONGITUDINAL MULTI-CENTER RCT COHORT OF R-AXSPA-PATIENTS WITH A HIGH RISK OF STRUCTURAL PROGRESSION INITIATING TREATMENT WITH TNF-INHIBITOR
Authors: C. E. Mistegaard, A. Troldborg, A. G. Loft, S. Thiel, B. Muche, V. Rios Rodriguez, M. Torgutalp, M. Protopopov, J. Listing, J. Sieper, D. Poddubnyy, F. Proft
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The pathogenesis of axial spondyloarthritis (axSpA) remains largely unexplained, but recent evidence supports an involvement of the innate immune system. The lectin pathway (LP) of complement activation plays an essential role in innate immunity. Previous studies have shown that elevated levels of specific complement proteins are associated with disease activity in axSpA. However, little is known about alterations in LP proteins and complement activation in relation to treatment with TNF-inhibitors (TNF-I). <h3>Objectives</h3> To determine changes in LP protein levels and complement activation in a longitudinal multi-center cohort of axSpA-patients with high disease activity from the RCT CONSUL before and after 12 weeks of treatment with a TNF-I. Furthermore, to investigate the correlations between LP protein levels, and disease activity, and treatment response. <h3>Methods</h3> Serum samples at baseline and after 12 weeks of treatment with the TNF-I golimumab were obtained from 108 radiographic axSpA-patients with high disease activity (BASDAI ≥4) and high risk for radiographic progression (elevated CRP or ≥1 syndesmophyte present at inclusion) recruited from the CONSUL cohort. Serum levels of the LP proteins MBL, CL-L1, H-ficolin, L-ficolin, M-ficolin, MASP-1, MASP-2, MASP-3, and MAp44, and complement activation product C3dg were measured by immunoassays. <h3>Results</h3> Serum levels of L-ficolin, M-ficolin, MBL, MAp44, and C3dg decreased significantly after 12 weeks of treatment with TNF-I, whereas serum levels of MASP-3 and CL-L1 increased significantly (Figure 1). After adjustment for CRP, significant changes were observed for L-ficolin, M-ficolin, MASP-1, MASP-2, MASP-3, and MAp44. Baseline serum levels of L-ficolin, M-ficolin, and C3dg correlated positively with baseline ASDAS-CRP (Spearman's rho 0.290, 0.190, and 0.328, respectively, all <i>p</i>&lt;0.05), whereas baseline MASP-1 and MAp44 correlated negatively with baseline ASDAS-CRP (Spearman's rho -0.204, and -0.218, respectively, both <i>p</i>&lt;0.05). In a univariate logistic regression analysis, baseline serum levels of MASP-1 predicted achievement of clinical important improvement (ΔASDAS≥1.1) at week 12, and baseline serum levels of C3dg predicted inactive disease (ASDAS&lt;1.3) at week 12. In corresponding multivariate logistic regression analyses, only C3dg remained significantly associated with inactive disease (ASDAS&lt;1.3) (<i>p</i> = 0.025). <h3>Conclusion</h3> Baseline serum levels of L-ficolin, M-ficolin and C3dg correlated positively with baseline ASDAS-CRP, and the protein serum levels decreased significantly after TNF-I therapy. Baseline levels of complement activation measured by C3dg predicted achievement of inactive disease (ASDAS&lt;1.3) at week 12 in both a univariate and a multivariate logistic regression analysis. Our findings suggest an involvement of the complement system in the underlying inflammatory processes of axSpA and prompt further investigations. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Clara Elbæk Mistegaard: None declared, Anne Troldborg: None declared, Anne Gitte Loft Speakers bureau: AbbVie, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, MSD, Novartis, Pfizer, and UCB, Grant/research support from: Novartis, Steffen Thiel: None declared, Burkhard Muche: None declared, Valeria Rios Rodriguez: None declared, Murat Torgutalp: None declared, Mikhail Protopopov: None declared, Joachim Listing: None declared, Joachim Sieper: None declared, Denis Poddubnyy: None declared, Fabian Proft Speakers bureau: AbbVie, AMGEN, BMS, Celgene, Hexal, Janssen, MSD, Novartis, Pfizer, Roche und UCB, Consultant of: AbbVie, AMGEN, BMS, Celgene, Hexal, Janssen, MSD, Novartis, Pfizer, Roche und UCB, Grant/research support from: Novartis, Eli Lilly and UCB.